Bibliography

Summary

One of the motivating factors behind research into cyclic peptides is
their application as scaffolds for the development of bioactive drugs.
As we have seen, the cyclotides exhibit a compact, rigid and stable
fold and would appear to be ideal for the engineering of novel
bioactive moieties. To accomplish this goal an understanding of the
way the CCK fold is affected by variations in loop composition and
length will be crucial. For example the haemolytic activity of the
cyclotides is an undesirable trait from a drug development perspective
and the abolition of this activity is a priority for the development
process. However it has been shown that the hydrophobic patch of the
cyclotides may stabilise the fold and the engineering of less
hydrophobic cyclotides may result in the loss of stability. To
explore the limits of the CCK fold two pathways can be followed -- the
synthesis of novel peptides or, given the ever expanding rate of
cyclotide discovery, the screening of a wide number of plants to
discover unusual cyclotides with atypical characteristics.

The evolution of the cyclotides presents a mystery. As discussed the
unusual distribution of the cyclotides suggests that the cyclotides
are either more prevalent than previously thought or have been lost in
the majority of plants. Also of interest is what, if any,
evolutionary relationship exists between the cyclotides and the other
ICK-containing proteins.

A key research goal in the field of cyclic peptides is the
determination of their biosynthesis and the cyclotides are not the
only cyclic peptides that are found in the plant kingdom. As the
biosynthesis of these peptides is so poorly understood it is not
possible to say whether there is a unifying cyclising process or
whether cyclisation can occur in a number of different ways. As
mentioned previously a recurring theme that will develop through this
section is the involvement of proteases in the processing of linear
precursors into mature cyclic peptides and the most compelling
evidence for this is the existence of the small trypsin inhibitor
SFTI-1 from the seeds of the sunflower. In the next section this
fascinating peptide will be examined and the key role that proteases
have played in cyclising this peptide in vitro reviewed.

CyBase is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.

The database and computational tools found on this website may be used for academic research only, provided that it is referred to CyBase, the database of cyclic proteins (http://www.cybase.org.au). For any other use please contact David Craik (d.craik@imb.uq.edu.au).